Disease modeling using human iPSCs starts by deriving iPSCs containing the disease-causing mutation(s) (Fig. 1). These cells are then differentiated into disease-relevant cell types. The resultant cells are used to reveal disease etiology and identify pathological mechanisms. In early studies of iPSC-based disease modeling, iPSCs derived from non-disease-affected individuals were used as controls for patient-derived iPSCs. However, like other cells, iPSCs have exhibited line-to-line variations, which complicates data interpretation because one has to distinguish the line-to-line variation from the true disease-relevant phenotypes.
